Adjuvants that stimulate TLR3 or NLPR3 pathways enhance the efficiency of influenza virus-like particle vaccines in aged mice

Abstract

There is intense interest in the design and use of vaccine strategies against influenza to enhance protective immune responses in the elderly. To address the need for improved influenza vaccines for the aged, two inflammatory adjuvants, Imject(®) alum (a stimulator of the Nod-like receptor, Nalp3) and poly I:C (a toll-like receptor type 3 ligand), were used during vaccination with novel influenza virus-like particles (VLP). Adult (4 month old) or aged (24 month old) mice were vaccinated with VLPs alone or in combination with adjuvant. VLP-vaccinated adult mice were protected from a lethal influenza virus challenge without the use of either adjuvant. In contrast, only aged mice that were vaccinated with VLPs plus adjuvant survived challenge, whereas ∼33% of the mice vaccinated with VLP only survived challenge. Mice vaccinated with adjuvant only did not survive challenge despite similar levels of activation of CD11b(+)/CD11c(+) dendritic cells in the lungs. The protection was not associated with HAI titers or HA specific CD8(+) T cells, since both adjuvants boosted the VLP-induced serum HAI titers and CD8(+) responses in adult mice, but not aged mice. Influenza VLPs used in combination with two different inflammatory adjuvants during vaccination allow for the immune system to overcome the deficiency in the aged immune system to influenza virus infection.